MMRd Project Update

1. Baseline Characteristics

1.1 With original MMRd types

	? (N=5)	Complex (N=11)	MLH1_PMS2 (N=251)	MSH2_MSH6 (N=70)	MSH6 (N=12)	NORMAL (N=19)	PMS2 (N=13)	Total (N=381)
Age (years)
Mean (SD)	64.4 (12.8)	63.8 (19.9)	67.9 (13.2)	56.8 (14.1)	64.5 (11.2)	61.1 (14.5)	54.3 (16.7)	64.8 (14.4)
Median [Min, Max]	63.0 [46.0, 77.0]	70.0 [26.0, 88.0]	71.0 [25.0, 90.0]	55.0 [30.0, 90.0]	67.0 [36.0, 76.0]	65.0 [31.0, 87.0]	48.0 [37.0, 84.0]	67.0 [25.0, 90.0]
Race
BLACK OR AFRICAN AMERICAN	1 (20.0%)	0 (0%)	15 (6.0%)	4 (5.7%)	0 (0%)	1 (5.3%)	1 (7.7%)	22 (5.8%)
PT REFUSED TO ANSWER	1 (20.0%)	0 (0%)	6 (2.4%)	1 (1.4%)	0 (0%)	1 (5.3%)	0 (0%)	9 (2.4%)
WHITE	3 (60.0%)	8 (72.7%)	208 (82.9%)	57 (81.4%)	10 (83.3%)	16 (84.2%)	9 (69.2%)	311 (81.6%)
ASIAN-FAR EAST/INDIAN SUBCONT	0 (0%)	2 (18.2%)	11 (4.4%)	4 (5.7%)	1 (8.3%)	1 (5.3%)	3 (23.1%)	22 (5.8%)
OTHER	0 (0%)	1 (9.1%)	9 (3.6%)	4 (5.7%)	1 (8.3%)	0 (0%)	0 (0%)	15 (3.9%)
NATIVE AMERICAN-AM IND/ALASKA	0 (0%)	0 (0%)	2 (0.8%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	2 (0.5%)
Ethnicity
Non-Spanish; Non-Hispanic	5 (100%)	8 (72.7%)	215 (85.7%)	58 (82.9%)	11 (91.7%)	18 (94.7%)	11 (84.6%)	326 (85.6%)
"Spanish NOS; Hispanic NOS, Latino NOS"	0 (0%)	2 (18.2%)	14 (5.6%)	8 (11.4%)	1 (8.3%)	1 (5.3%)	1 (7.7%)	27 (7.1%)
Dominican Republic	0 (0%)	1 (9.1%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	1 (0.3%)
0	0 (0%)	0 (0%)	3 (1.2%)	2 (2.9%)	0 (0%)	0 (0%)	0 (0%)	5 (1.3%)
Puerto Rican	0 (0%)	0 (0%)	2 (0.8%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	2 (0.5%)
Unknown whether Spanish or not	0 (0%)	0 (0%)	17 (6.8%)	2 (2.9%)	0 (0%)	0 (0%)	1 (7.7%)	20 (5.2%)
Tumor Purity (%)
Mean (SD)	48.0 (19.2)	38.2 (12.7)	38.3 (16.0)	39.6 (15.8)	39.6 (16.3)	47.2 (17.0)	38.8 (19.4)	39.2 (16.1)
Median [Min, Max]	50.0 [20.0, 70.0]	30.0 [25.0, 60.0]	40.0 [10.0, 90.0]	40.0 [5.00, 80.0]	30.0 [25.0, 80.0]	50.0 [20.0, 70.0]	35.0 [10.0, 70.0]	40.0 [5.00, 90.0]
Missing	0 (0%)	0 (0%)	1 (0.4%)	2 (2.9%)	0 (0%)	0 (0%)	0 (0%)	3 (0.8%)
Cancer Type
Bladder	1 (20.0%)	0 (0%)	0 (0%)	5 (7.1%)	2 (16.7%)	0 (0%)	1 (7.7%)	9 (2.4%)
Endometrial	1 (20.0%)	1 (9.1%)	62 (24.7%)	14 (20.0%)	1 (8.3%)	4 (21.1%)	0 (0%)	83 (21.8%)
Esophagogastric	2 (40.0%)	1 (9.1%)	33 (13.1%)	4 (5.7%)	0 (0%)	2 (10.5%)	0 (0%)	42 (11.0%)
Small Bowel	1 (20.0%)	0 (0%)	4 (1.6%)	2 (2.9%)	0 (0%)	1 (5.3%)	4 (30.8%)	12 (3.1%)
Colon	0 (0%)	9 (81.8%)	118 (47.0%)	19 (27.1%)	4 (33.3%)	7 (36.8%)	4 (30.8%)	161 (42.3%)
Biliary	0 (0%)	0 (0%)	5 (2.0%)	0 (0%)	0 (0%)	0 (0%)	1 (7.7%)	6 (1.6%)
Colorectal	0 (0%)	0 (0%)	10 (4.0%)	5 (7.1%)	3 (25.0%)	4 (21.1%)	1 (7.7%)	23 (6.0%)
CUP	0 (0%)	0 (0%)	5 (2.0%)	0 (0%)	0 (0%)	1 (5.3%)	0 (0%)	6 (1.6%)
Other	0 (0%)	0 (0%)	2 (0.8%)	5 (7.1%)	0 (0%)	0 (0%)	0 (0%)	7 (1.8%)
Ovarian	0 (0%)	0 (0%)	1 (0.4%)	2 (2.9%)	0 (0%)	0 (0%)	1 (7.7%)	4 (1.0%)
Pancreas	0 (0%)	0 (0%)	1 (0.4%)	2 (2.9%)	1 (8.3%)	0 (0%)	0 (0%)	4 (1.0%)
Prostate	0 (0%)	0 (0%)	1 (0.4%)	2 (2.9%)	1 (8.3%)	0 (0%)	0 (0%)	4 (1.0%)
Rectal	0 (0%)	0 (0%)	9 (3.6%)	10 (14.3%)	0 (0%)	0 (0%)	1 (7.7%)	20 (5.2%)
Sample Type
Metastasis	1 (20.0%)	1 (9.1%)	29 (11.6%)	6 (8.6%)	2 (16.7%)	4 (21.1%)	2 (15.4%)	45 (11.8%)
Mixed	1 (20.0%)	1 (9.1%)	17 (6.8%)	5 (7.1%)	2 (16.7%)	1 (5.3%)	1 (7.7%)	28 (7.3%)
Primary	3 (60.0%)	9 (81.8%)	205 (81.7%)	59 (84.3%)	8 (66.7%)	14 (73.7%)	10 (76.9%)	308 (80.8%)

1.2 With MMRd types collapsed by Multiplex or not

	Singleton (N=25)	? (N=5)	Multiplex (N=332)	NORMAL (N=19)	Total (N=381)
Age (years)
Mean (SD)	59.2 (15.0)	64.4 (12.8)	65.4 (14.3)	61.1 (14.5)	64.8 (14.4)
Median [Min, Max]	64.0 [36.0, 84.0]	63.0 [46.0, 77.0]	68.0 [25.0, 90.0]	65.0 [31.0, 87.0]	67.0 [25.0, 90.0]
Race
ASIAN-FAR EAST/INDIAN SUBCONT	4 (16.0%)	0 (0%)	17 (5.1%)	1 (5.3%)	22 (5.8%)
BLACK OR AFRICAN AMERICAN	1 (4.0%)	1 (20.0%)	19 (5.7%)	1 (5.3%)	22 (5.8%)
OTHER	1 (4.0%)	0 (0%)	14 (4.2%)	0 (0%)	15 (3.9%)
WHITE	19 (76.0%)	3 (60.0%)	273 (82.2%)	16 (84.2%)	311 (81.6%)
PT REFUSED TO ANSWER	0 (0%)	1 (20.0%)	7 (2.1%)	1 (5.3%)	9 (2.4%)
NATIVE AMERICAN-AM IND/ALASKA	0 (0%)	0 (0%)	2 (0.6%)	0 (0%)	2 (0.5%)
Ethnicity
"Spanish NOS; Hispanic NOS, Latino NOS"	2 (8.0%)	0 (0%)	24 (7.2%)	1 (5.3%)	27 (7.1%)
Non-Spanish; Non-Hispanic	22 (88.0%)	5 (100%)	281 (84.6%)	18 (94.7%)	326 (85.6%)
Unknown whether Spanish or not	1 (4.0%)	0 (0%)	19 (5.7%)	0 (0%)	20 (5.2%)
0	0 (0%)	0 (0%)	5 (1.5%)	0 (0%)	5 (1.3%)
Dominican Republic	0 (0%)	0 (0%)	1 (0.3%)	0 (0%)	1 (0.3%)
Puerto Rican	0 (0%)	0 (0%)	2 (0.6%)	0 (0%)	2 (0.5%)
Tumor Purity (%)
Mean (SD)	39.2 (17.6)	48.0 (19.2)	38.6 (15.8)	47.2 (17.0)	39.2 (16.1)
Median [Min, Max]	30.0 [10.0, 80.0]	50.0 [20.0, 70.0]	40.0 [5.00, 90.0]	50.0 [20.0, 70.0]	40.0 [5.00, 90.0]
Missing	0 (0%)	0 (0%)	3 (0.9%)	0 (0%)	3 (0.8%)
Cancer Type
Colon	8 (32.0%)	0 (0%)	146 (44.0%)	7 (36.8%)	161 (42.3%)
Biliary	1 (4.0%)	0 (0%)	5 (1.5%)	0 (0%)	6 (1.6%)
Bladder	3 (12.0%)	1 (20.0%)	5 (1.5%)	0 (0%)	9 (2.4%)
Colorectal	4 (16.0%)	0 (0%)	15 (4.5%)	4 (21.1%)	23 (6.0%)
CUP	0 (0%)	0 (0%)	5 (1.5%)	1 (5.3%)	6 (1.6%)
Endometrial	1 (4.0%)	1 (20.0%)	77 (23.2%)	4 (21.1%)	83 (21.8%)
Esophagogastric	0 (0%)	2 (40.0%)	38 (11.4%)	2 (10.5%)	42 (11.0%)
Other	0 (0%)	0 (0%)	7 (2.1%)	0 (0%)	7 (1.8%)
Ovarian	1 (4.0%)	0 (0%)	3 (0.9%)	0 (0%)	4 (1.0%)
Pancreas	1 (4.0%)	0 (0%)	3 (0.9%)	0 (0%)	4 (1.0%)
Prostate	1 (4.0%)	0 (0%)	3 (0.9%)	0 (0%)	4 (1.0%)
Rectal	1 (4.0%)	0 (0%)	19 (5.7%)	0 (0%)	20 (5.2%)
Small Bowel	4 (16.0%)	1 (20.0%)	6 (1.8%)	1 (5.3%)	12 (3.1%)
Sample Type
Metastasis	4 (16.0%)	1 (20.0%)	36 (10.8%)	4 (21.1%)	45 (11.8%)
Mixed	3 (12.0%)	1 (20.0%)	23 (6.9%)	1 (5.3%)	28 (7.3%)
Primary	18 (72.0%)	3 (60.0%)	273 (82.2%)	14 (73.7%)	308 (80.8%)

1.3 With MMRd types collapsed by MSH6 or not

	MSH6 (N=82)	Not_MSH6 (N=299)	Total (N=381)
Age (years)
Mean (SD)	57.9 (13.9)	66.6 (14.0)	64.8 (14.4)
Median [Min, Max]	56.5 [30.0, 90.0]	70.0 [25.0, 90.0]	67.0 [25.0, 90.0]
Race
ASIAN-FAR EAST/INDIAN SUBCONT	5 (6.1%)	17 (5.7%)	22 (5.8%)
BLACK OR AFRICAN AMERICAN	4 (4.9%)	18 (6.0%)	22 (5.8%)
OTHER	5 (6.1%)	10 (3.3%)	15 (3.9%)
PT REFUSED TO ANSWER	1 (1.2%)	8 (2.7%)	9 (2.4%)
WHITE	67 (81.7%)	244 (81.6%)	311 (81.6%)
NATIVE AMERICAN-AM IND/ALASKA	0 (0%)	2 (0.7%)	2 (0.5%)
Ethnicity
"Spanish NOS; Hispanic NOS, Latino NOS"	9 (11.0%)	18 (6.0%)	27 (7.1%)
0	2 (2.4%)	3 (1.0%)	5 (1.3%)
Non-Spanish; Non-Hispanic	69 (84.1%)	257 (86.0%)	326 (85.6%)
Unknown whether Spanish or not	2 (2.4%)	18 (6.0%)	20 (5.2%)
Dominican Republic	0 (0%)	1 (0.3%)	1 (0.3%)
Puerto Rican	0 (0%)	2 (0.7%)	2 (0.5%)
Tumor Purity (%)
Mean (SD)	39.6 (15.8)	39.1 (16.2)	39.2 (16.1)
Median [Min, Max]	40.0 [5.00, 80.0]	40.0 [10.0, 90.0]	40.0 [5.00, 90.0]
Missing	2 (2.4%)	1 (0.3%)	3 (0.8%)
Cancer Type
Colon	23 (28.0%)	138 (46.2%)	161 (42.3%)
Biliary	0 (0%)	6 (2.0%)	6 (1.6%)
Bladder	7 (8.5%)	2 (0.7%)	9 (2.4%)
Colorectal	8 (9.8%)	15 (5.0%)	23 (6.0%)
CUP	0 (0%)	6 (2.0%)	6 (1.6%)
Endometrial	15 (18.3%)	68 (22.7%)	83 (21.8%)
Esophagogastric	4 (4.9%)	38 (12.7%)	42 (11.0%)
Other	5 (6.1%)	2 (0.7%)	7 (1.8%)
Ovarian	2 (2.4%)	2 (0.7%)	4 (1.0%)
Pancreas	3 (3.7%)	1 (0.3%)	4 (1.0%)
Prostate	3 (3.7%)	1 (0.3%)	4 (1.0%)
Rectal	10 (12.2%)	10 (3.3%)	20 (5.2%)
Small Bowel	2 (2.4%)	10 (3.3%)	12 (3.1%)
Sample Type
Metastasis	8 (9.8%)	37 (12.4%)	45 (11.8%)
Mixed	7 (8.5%)	21 (7.0%)	28 (7.3%)
Primary	67 (81.7%)	241 (80.6%)	308 (80.8%)

1.4With MMRd types collapsed by PMS2 or not

	PMS2 (N=264)	Not_PMS2 (N=117)	Total (N=381)
Age (years)
Mean (SD)	67.2 (13.7)	59.3 (14.6)	64.8 (14.4)
Median [Min, Max]	70.0 [25.0, 90.0]	59.0 [26.0, 90.0]	67.0 [25.0, 90.0]
Race
ASIAN-FAR EAST/INDIAN SUBCONT	14 (5.3%)	8 (6.8%)	22 (5.8%)
BLACK OR AFRICAN AMERICAN	16 (6.1%)	6 (5.1%)	22 (5.8%)
NATIVE AMERICAN-AM IND/ALASKA	2 (0.8%)	0 (0%)	2 (0.5%)
OTHER	9 (3.4%)	6 (5.1%)	15 (3.9%)
PT REFUSED TO ANSWER	6 (2.3%)	3 (2.6%)	9 (2.4%)
WHITE	217 (82.2%)	94 (80.3%)	311 (81.6%)
Ethnicity
"Spanish NOS; Hispanic NOS, Latino NOS"	15 (5.7%)	12 (10.3%)	27 (7.1%)
0	3 (1.1%)	2 (1.7%)	5 (1.3%)
Non-Spanish; Non-Hispanic	226 (85.6%)	100 (85.5%)	326 (85.6%)
Puerto Rican	2 (0.8%)	0 (0%)	2 (0.5%)
Unknown whether Spanish or not	18 (6.8%)	2 (1.7%)	20 (5.2%)
Dominican Republic	0 (0%)	1 (0.9%)	1 (0.3%)
Tumor Purity (%)
Mean (SD)	38.3 (16.1)	41.1 (16.0)	39.2 (16.1)
Median [Min, Max]	40.0 [10.0, 90.0]	40.0 [5.00, 80.0]	40.0 [5.00, 90.0]
Missing	1 (0.4%)	2 (1.7%)	3 (0.8%)
Cancer Type
Colon	122 (46.2%)	39 (33.3%)	161 (42.3%)
Biliary	6 (2.3%)	0 (0%)	6 (1.6%)
Bladder	1 (0.4%)	8 (6.8%)	9 (2.4%)
Colorectal	11 (4.2%)	12 (10.3%)	23 (6.0%)
CUP	5 (1.9%)	1 (0.9%)	6 (1.6%)
Endometrial	62 (23.5%)	21 (17.9%)	83 (21.8%)
Esophagogastric	33 (12.5%)	9 (7.7%)	42 (11.0%)
Other	2 (0.8%)	5 (4.3%)	7 (1.8%)
Ovarian	2 (0.8%)	2 (1.7%)	4 (1.0%)
Pancreas	1 (0.4%)	3 (2.6%)	4 (1.0%)
Prostate	1 (0.4%)	3 (2.6%)	4 (1.0%)
Rectal	10 (3.8%)	10 (8.5%)	20 (5.2%)
Small Bowel	8 (3.0%)	4 (3.4%)	12 (3.1%)
Sample Type
Metastasis	31 (11.7%)	14 (12.0%)	45 (11.8%)
Mixed	18 (6.8%)	10 (8.5%)	28 (7.3%)
Primary	215 (81.4%)	93 (79.5%)	308 (80.8%)

2. Linear Mixed Effect Regression Model to predict the genomic features with original MMRd types

Apply a statistical model to predict genomic features with multiple fixed effects,

MMRd Types, Cancer Types, Age, Tumor purity, Race and more, adjusting for random effects like Metastatic status

#####Groups: Complex, MSH2_MSH6, MLH1_PMS2, MSH6, PMS2, Normal

#####Formula: Feautre ~ MMRd.Type +/* Cancer.Type + Age + Tumor.purity + Race + (1 + MMRd.Type | Metastatic.status)

3. Linear Mixed Effect Regression Model to predict the genomic features with collapsed MMRd types

Apply a statistical model to predict genomic features with multiple fixed effects,

MMRd Types(collapsed), Cancer Types, Age, Tumor purity, Race and more, adjusting for random effects like Metastatic status

3.1 Significances By collapsed Multiplex or not

#####Groups: 1) Singleton: MSH6, PMS2; 2) Multiplex: MSH2_MSH6, MLH1_PMS2, Complex; 3) Normal;

#####Formula: Feautre ~ Multiplex_or_not +/* Cancer.Type + Age + Tumor.purity + Race + (1 + Multiplex_or_not | Metastatic.status)

3.2 Significances By collapsed MSH6 or not

#####Groups: 1) MSH6: MSH2_MSH6, MSH6; 2) Not_MSH6: MLH1_PMS2, PMS2, Normal

#####Formula: Feautre ~ MSH6_or_not +/* Cancer.Type + Age + Tumor.purity + Race + (1 + MSH6_or_not | Metastatic.status)

3.3 Significances By collapsed PMS2 or not

#####Groups: 1) PMS2: MLH1_PMS2, PMS2; 2) Not_PMS2: MSH2_MSH6, MSH6, Normal

Feautre ~ PMS2_or_not +/* Cancer.Type + Age + Tumor.purity + Race + (1 + PMS2_or_not | Metastatic.status)

4. Survival Plots with all MMRd and Cancer types

• 4.1 Plot OS difference between original/collapsed MMRd types (e.g.: Multiplex vs Singleton; MSH6 vs Non_MSH6; PMS2 vs Non_PMS2), across all or most populated cancer types (e.g. “Colon”, “Endometrial”, “Esophagogastric”)
• 4.2 Plot OS difference between Y/N of oncogenic mutations in the genes (e.g.: TP53, KRAS, BRAF, RNF43)

5 Aneuploidy Analysis

6. Luiz permbro-treated WES Data

6.1 Baseline Characteristics

	MSH2_MSH6 (N=9)	MLH1_PMS2 (N=9)	PMS2 (N=1)	MSH6 (N=2)	? (N=7)	Total (N=28)
Age
Mean (SD)	50.6 (16.1)	50.4 (11.9)	50.0 (NA)	53.5 (2.12)	53.4 (9.80)	51.4 (11.9)
Median [Min, Max]	57.0 [29.0, 71.0]	52.0 [24.0, 64.0]	50.0 [50.0, 50.0]	53.5 [52.0, 55.0]	52.0 [39.0, 67.0]	52.0 [24.0, 71.0]
Gender
Female	2 (22.2%)	4 (44.4%)	0 (0%)	0 (0%)	5 (71.4%)	11 (39.3%)
Male	7 (77.8%)	5 (55.6%)	1 (100%)	2 (100%)	2 (28.6%)	17 (60.7%)
Race
Asian	1 (11.1%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	1 (3.6%)
White	8 (88.9%)	8 (88.9%)	1 (100%)	2 (100%)	5 (71.4%)	24 (85.7%)
Unknown	0 (0%)	1 (11.1%)	0 (0%)	0 (0%)	0 (0%)	1 (3.6%)
Black or African American	0 (0%)	0 (0%)	0 (0%)	0 (0%)	2 (28.6%)	2 (7.1%)
Ethnicity
non-Hispanic	9 (100%)	7 (77.8%)	1 (100%)	2 (100%)	7 (100%)	26 (92.9%)
Hispanic	0 (0%)	2 (22.2%)	0 (0%)	0 (0%)	0 (0%)	2 (7.1%)
Lynch.Clinical
No	1 (11.1%)	4 (44.4%)	0 (0%)	0 (0%)	2 (28.6%)	7 (25.0%)
UNK	0 (0%)	1 (11.1%)	0 (0%)	0 (0%)	1 (14.3%)	2 (7.1%)
Yes	8 (88.9%)	4 (44.4%)	1 (100%)	2 (100%)	4 (57.1%)	19 (67.9%)
TumorType
Ampulla of Vater	2 (22.2%)	0 (0%)	0 (0%)	1 (50.0%)	0 (0%)	3 (10.7%)
Cholangiocarcinoma	1 (11.1%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	1 (3.6%)
Colorectal	3 (33.3%)	7 (77.8%)	0 (0%)	0 (0%)	5 (71.4%)	15 (53.6%)
Endometrial cancer	1 (11.1%)	1 (11.1%)	0 (0%)	0 (0%)	2 (28.6%)	4 (14.3%)
Gastroesophageal cancer	1 (11.1%)	0 (0%)	1 (100%)	0 (0%)	0 (0%)	2 (7.1%)
Small Intestine	1 (11.1%)	1 (11.1%)	0 (0%)	0 (0%)	0 (0%)	2 (7.1%)
Thyroid	0 (0%)	0 (0%)	0 (0%)	1 (50.0%)	0 (0%)	1 (3.6%)
Assembly
hg18	7 (77.8%)	5 (55.6%)	0 (0%)	1 (50.0%)	5 (71.4%)	18 (64.3%)
hg19	2 (22.2%)	4 (44.4%)	1 (100%)	1 (50.0%)	2 (28.6%)	10 (35.7%)

6.2 Genomic Feature Exploration

	MSH2_MSH6				MLH1_PMS2				PMS2	MSH6	Overall
	PD (N=4)	SD (N=1)	PR (N=1)	CR (N=3)	PD (N=1)	SD (N=2)	PR (N=4)	CR (N=2)	PD (N=1)	NE (N=2)	NE (N=2)	PD (N=6)	SD (N=3)	PR (N=5)	CR (N=5)
Stop_variant
Mean (SD)	0 (0)	0 (NA)	0 (NA)	0 (0)	0 (NA)	0 (0)	0 (0)	0 (0)	1.00 (NA)	0 (0)	0 (0)	0.167 (0.408)	0 (0)	0 (0)	0 (0)
Median [Min, Max]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	1.00 [1.00, 1.00]	0 [0, 0]	0 [0, 0]	0 [0, 1.00]	0 [0, 0]	0 [0, 0]	0 [0, 0]
Start_variant
Mean (SD)	0 (0)	1.00 (NA)	0 (NA)	0 (0)	0 (NA)	0.500 (0.707)	0 (0)	0 (0)	0 (NA)	0 (0)	0 (0)	0 (0)	0.667 (0.577)	0 (0)	0 (0)
Median [Min, Max]	0 [0, 0]	1.00 [1.00, 1.00]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0.500 [0, 1.00]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	1.00 [0, 1.00]	0 [0, 0]	0 [0, 0]
Splice_site_donor
Mean (SD)	22.5 (11.8)	88.0 (NA)	11.0 (NA)	89.3 (72.5)	6.00 (NA)	23.5 (21.9)	36.0 (7.87)	25.0 (5.66)	22.0 (NA)	24.5 (0.707)	24.5 (0.707)	19.7 (11.3)	45.0 (40.3)	31.0 (13.1)	63.6 (62.3)
Median [Min, Max]	27.5 [5.00, 30.0]	88.0 [88.0, 88.0]	11.0 [11.0, 11.0]	49.0 [46.0, 173]	6.00 [6.00, 6.00]	23.5 [8.00, 39.0]	36.5 [26.0, 45.0]	25.0 [21.0, 29.0]	22.0 [22.0, 22.0]	24.5 [24.0, 25.0]	24.5 [24.0, 25.0]	24.0 [5.00, 30.0]	39.0 [8.00, 88.0]	35.0 [11.0, 45.0]	46.0 [21.0, 173]
Splice_site_acceptor
Mean (SD)	103 (68.1)	22.0 (NA)	33.0 (NA)	202 (5.86)	11.0 (NA)	80.0 (103)	152 (34.2)	119 (4.95)	24.0 (NA)	68.5 (50.2)	68.5 (50.2)	74.7 (69.0)	60.7 (80.3)	128 (60.7)	169 (46.2)
Median [Min, Max]	129 [5.00, 151]	22.0 [22.0, 22.0]	33.0 [33.0, 33.0]	200 [198, 209]	11.0 [11.0, 11.0]	80.0 [7.00, 153]	155 [110, 186]	119 [115, 122]	24.0 [24.0, 24.0]	68.5 [33.0, 104]	68.5 [33.0, 104]	67.0 [5.00, 151]	22.0 [7.00, 153]	138 [33.0, 186]	198 [115, 209]
Nonsynonymous_coding
Mean (SD)	845 (423)	3240 (NA)	203 (NA)	2100 (1230)	374 (NA)	1950 (1300)	720 (199)	574 (120)	1260 (NA)	1360 (757)	1360 (757)	835 (431)	2380 (1180)	616 (288)	1490 (1210)
Median [Min, Max]	728 [472, 1450]	3240 [3240, 3240]	203 [203, 203]	1410 [1360, 3520]	374 [374, 374]	1950 [1030, 2870]	746 [455, 932]	574 [489, 658]	1260 [1260, 1260]	1360 [820, 1890]	1360 [820, 1890]	728 [374, 1450]	2870 [1030, 3240]	710 [203, 932]	1360 [489, 3520]
Nonsense
Mean (SD)	45.8 (31.1)	65.0 (NA)	10.0 (NA)	88.7 (15.8)	20.0 (NA)	47.0 (32.5)	35.5 (14.2)	36.0 (18.4)	53.0 (NA)	67.0 (49.5)	67.0 (49.5)	42.7 (26.7)	53.0 (25.2)	30.4 (16.8)	67.6 (32.3)
Median [Min, Max]	37.0 [19.0, 90.0]	65.0 [65.0, 65.0]	10.0 [10.0, 10.0]	85.0 [75.0, 106]	20.0 [20.0, 20.0]	47.0 [24.0, 70.0]	34.0 [20.0, 54.0]	36.0 [23.0, 49.0]	53.0 [53.0, 53.0]	67.0 [32.0, 102]	67.0 [32.0, 102]	37.0 [19.0, 90.0]	65.0 [24.0, 70.0]	31.0 [10.0, 54.0]	75.0 [23.0, 106]
Inframe_Ins
Mean (SD)	2.00 (2.71)	1.00 (NA)	0 (NA)	7.33 (2.52)	1.00 (NA)	7.50 (2.12)	3.50 (0.577)	4.00 (0)	1.00 (NA)	1.00 (1.41)	1.00 (1.41)	1.67 (2.16)	5.33 (4.04)	2.80 (1.64)	6.00 (2.55)
Median [Min, Max]	1.00 [0, 6.00]	1.00 [1.00, 1.00]	0 [0, 0]	7.00 [5.00, 10.0]	1.00 [1.00, 1.00]	7.50 [6.00, 9.00]	3.50 [3.00, 4.00]	4.00 [4.00, 4.00]	1.00 [1.00, 1.00]	1.00 [0, 2.00]	1.00 [0, 2.00]	1.00 [0, 6.00]	6.00 [1.00, 9.00]	3.00 [0, 4.00]	5.00 [4.00, 10.0]
Inframe_Del
Mean (SD)	14.0 (11.3)	5.00 (NA)	5.00 (NA)	30.3 (2.52)	9.00 (NA)	23.0 (15.6)	20.8 (6.24)	20.5 (0.707)	17.0 (NA)	4.00 (1.41)	4.00 (1.41)	13.7 (9.16)	17.0 (15.1)	17.6 (8.88)	26.4 (5.68)
Median [Min, Max]	10.5 [5.00, 30.0]	5.00 [5.00, 5.00]	5.00 [5.00, 5.00]	30.0 [28.0, 33.0]	9.00 [9.00, 9.00]	23.0 [12.0, 34.0]	21.0 [14.0, 27.0]	20.5 [20.0, 21.0]	17.0 [17.0, 17.0]	4.00 [3.00, 5.00]	4.00 [3.00, 5.00]	11.5 [5.00, 30.0]	12.0 [5.00, 34.0]	17.0 [5.00, 27.0]	28.0 [20.0, 33.0]
Frameshift
Mean (SD)	267 (131)	537 (NA)	105 (NA)	578 (75.6)	179 (NA)	273 (326)	388 (96.1)	293 (45.3)	536 (NA)	102 (91.2)	102 (91.2)	297 (159)	361 (276)	331 (151)	464 (167)
Median [Min, Max]	278 [125, 386]	537 [537, 537]	105 [105, 105]	621 [491, 623]	179 [179, 179]	273 [42.0, 503]	394 [273, 489]	293 [261, 325]	536 [536, 536]	102 [37.0, 166]	102 [37.0, 166]	278 [125, 536]	503 [42.0, 537]	348 [105, 489]	491 [261, 623]

	NE	PD			SD		PR		CR		Overall
	MSH6 (N=2)	MSH2_MSH6 (N=4)	MLH1_PMS2 (N=1)	PMS2 (N=1)	MSH2_MSH6 (N=1)	MLH1_PMS2 (N=2)	MSH2_MSH6 (N=1)	MLH1_PMS2 (N=4)	MSH2_MSH6 (N=3)	MLH1_PMS2 (N=2)	MSH2_MSH6 (N=9)	MLH1_PMS2 (N=9)	PMS2 (N=1)	MSH6 (N=2)
Stop_variant
Mean (SD)	0 (0)	0 (0)	0 (NA)	1.00 (NA)	0 (NA)	0 (0)	0 (NA)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	1.00 (NA)	0 (0)
Median [Min, Max]	0 [0, 0]	0 [0, 0]	0 [0, 0]	1.00 [1.00, 1.00]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	1.00 [1.00, 1.00]	0 [0, 0]
Start_variant
Mean (SD)	0 (0)	0 (0)	0 (NA)	0 (NA)	1.00 (NA)	0.500 (0.707)	0 (NA)	0 (0)	0 (0)	0 (0)	0.111 (0.333)	0.111 (0.333)	0 (NA)	0 (0)
Median [Min, Max]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	1.00 [1.00, 1.00]	0.500 [0, 1.00]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 0]	0 [0, 1.00]	0 [0, 1.00]	0 [0, 0]	0 [0, 0]
Splice_site_donor
Mean (SD)	24.5 (0.707)	22.5 (11.8)	6.00 (NA)	22.0 (NA)	88.0 (NA)	23.5 (21.9)	11.0 (NA)	36.0 (7.87)	89.3 (72.5)	25.0 (5.66)	50.8 (51.9)	27.4 (13.7)	22.0 (NA)	24.5 (0.707)
Median [Min, Max]	24.5 [24.0, 25.0]	27.5 [5.00, 30.0]	6.00 [6.00, 6.00]	22.0 [22.0, 22.0]	88.0 [88.0, 88.0]	23.5 [8.00, 39.0]	11.0 [11.0, 11.0]	36.5 [26.0, 45.0]	49.0 [46.0, 173]	25.0 [21.0, 29.0]	30.0 [5.00, 173]	29.0 [6.00, 45.0]	22.0 [22.0, 22.0]	24.5 [24.0, 25.0]
Splice_site_acceptor
Mean (SD)	68.5 (50.2)	103 (68.1)	11.0 (NA)	24.0 (NA)	22.0 (NA)	80.0 (103)	33.0 (NA)	152 (34.2)	202 (5.86)	119 (4.95)	119 (81.1)	113 (64.0)	24.0 (NA)	68.5 (50.2)
Median [Min, Max]	68.5 [33.0, 104]	129 [5.00, 151]	11.0 [11.0, 11.0]	24.0 [24.0, 24.0]	22.0 [22.0, 22.0]	80.0 [7.00, 153]	33.0 [33.0, 33.0]	155 [110, 186]	200 [198, 209]	119 [115, 122]	147 [5.00, 209]	122 [7.00, 186]	24.0 [24.0, 24.0]	68.5 [33.0, 104]
Nonsynonymous_coding
Mean (SD)	1360 (757)	845 (423)	374 (NA)	1260 (NA)	3240 (NA)	1950 (1300)	203 (NA)	720 (199)	2100 (1230)	574 (120)	1460 (1170)	923 (763)	1260 (NA)	1360 (757)
Median [Min, Max]	1360 [820, 1890]	728 [472, 1450]	374 [374, 374]	1260 [1260, 1260]	3240 [3240, 3240]	1950 [1030, 2870]	203 [203, 203]	746 [455, 932]	1410 [1360, 3520]	574 [489, 658]	1360 [203, 3520]	710 [374, 2870]	1260 [1260, 1260]	1360 [820, 1890]
Nonsense
Mean (SD)	67.0 (49.5)	45.8 (31.1)	20.0 (NA)	53.0 (NA)	65.0 (NA)	47.0 (32.5)	10.0 (NA)	35.5 (14.2)	88.7 (15.8)	36.0 (18.4)	58.2 (33.9)	36.4 (17.7)	53.0 (NA)	67.0 (49.5)
Median [Min, Max]	67.0 [32.0, 102]	37.0 [19.0, 90.0]	20.0 [20.0, 20.0]	53.0 [53.0, 53.0]	65.0 [65.0, 65.0]	47.0 [24.0, 70.0]	10.0 [10.0, 10.0]	34.0 [20.0, 54.0]	85.0 [75.0, 106]	36.0 [23.0, 49.0]	65.0 [10.0, 106]	31.0 [20.0, 70.0]	53.0 [53.0, 53.0]	67.0 [32.0, 102]
Inframe_Ins
Mean (SD)	1.00 (1.41)	2.00 (2.71)	1.00 (NA)	1.00 (NA)	1.00 (NA)	7.50 (2.12)	0 (NA)	3.50 (0.577)	7.33 (2.52)	4.00 (0)	3.44 (3.64)	4.22 (2.22)	1.00 (NA)	1.00 (1.41)
Median [Min, Max]	1.00 [0, 2.00]	1.00 [0, 6.00]	1.00 [1.00, 1.00]	1.00 [1.00, 1.00]	1.00 [1.00, 1.00]	7.50 [6.00, 9.00]	0 [0, 0]	3.50 [3.00, 4.00]	7.00 [5.00, 10.0]	4.00 [4.00, 4.00]	1.00 [0, 10.0]	4.00 [1.00, 9.00]	1.00 [1.00, 1.00]	1.00 [0, 2.00]
Inframe_Del
Mean (SD)	4.00 (1.41)	14.0 (11.3)	9.00 (NA)	17.0 (NA)	5.00 (NA)	23.0 (15.6)	5.00 (NA)	20.8 (6.24)	30.3 (2.52)	20.5 (0.707)	17.4 (12.5)	19.9 (7.91)	17.0 (NA)	4.00 (1.41)
Median [Min, Max]	4.00 [3.00, 5.00]	10.5 [5.00, 30.0]	9.00 [9.00, 9.00]	17.0 [17.0, 17.0]	5.00 [5.00, 5.00]	23.0 [12.0, 34.0]	5.00 [5.00, 5.00]	21.0 [14.0, 27.0]	30.0 [28.0, 33.0]	20.5 [20.0, 21.0]	14.0 [5.00, 33.0]	20.0 [9.00, 34.0]	17.0 [17.0, 17.0]	4.00 [3.00, 5.00]
Frameshift
Mean (SD)	102 (91.2)	267 (131)	179 (NA)	536 (NA)	537 (NA)	273 (326)	105 (NA)	388 (96.1)	578 (75.6)	293 (45.3)	383 (204)	318 (150)	536 (NA)	102 (91.2)
Median [Min, Max]	102 [37.0, 166]	278 [125, 386]	179 [179, 179]	536 [536, 536]	537 [537, 537]	273 [42.0, 503]	105 [105, 105]	394 [273, 489]	621 [491, 623]	293 [261, 325]	386 [105, 623]	325 [42.0, 503]	536 [536, 536]	102 [37.0, 166]

6.3 Mutation Signatures

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